Different anesthetic preparations which are divided into narcotic (morphine and congenial structures) and non-narcotic analgesics (derivatives of salicylic acid, pyrazolone, aniline etc.) in terms of their chemical nature and mode of action are known. All the above mentioned analgesics have certain disadvantages which sharply narrow down possibilities of their application in medicine (M. D. Mashkovsky. Medicinal products, Kharkov: “Torsing” publishing house, 1997, edition 13, pp. 144-145).
The known peptide analgesics are synthetic analogs of natural enkephalins and endorphins, such as opioid peptides (Casy A. F., Parfitt A. C., Opioid analgesics: Chemistry and receptors. New York, Plenum Press, 1986, 445-502; Lierz P., Stefan Punsmann S., 2008). Their main disadvantage is that anesthetic activity is accompanied by habituation and narcotic action. Moreover, narcotic analgesics are not effective in all pain syndromes (Fallon M. When morphine does not work. Support Care Cancer. 2008 Feb. 15).
Peptide analgesics which have non-narcotic type of anesthesia not causing habituation and narcotic action are also known. Their anesthetic action is developed through non-opioid receptors and neurotransmitters. Synthetic and, more recently, recombinant calcitonins, anesthetic action of which is implemented through specific calcitonin receptors and brain serotonergic system, have gained the most widespread currency in that group (Yasushi Kuraishi/Neuropeptide action of calcitonin-analgesic effect/ in Magazine Kidney and Metabolic Bone Disease, V. 14 No 03). The most commonly used is synthetic sequence corresponding to salmon calcitonin as the most active one among all known calcitonins. Salmon calcitonin is a polypeptide hormone consisting of 32 residues of amino acids with molecular weight of 3,454.93 Dalton. Its structure represents an alpha helix (Andreotti G. et al, 2006).
Salmon calcitonin has long-term anesthetic action and presently exists in different pharmaceutical forms: in the form of spray or drops for intranasal use, oral and intramuscular administration, as well as in the form of suppositories.
However full-length calcitonins have a variety of essential disadvantages, including:
1) Hormonal activity, impact on calcium and phosphoric metabolism. In this connection calcitonins may not be used during pregnancy and labor pain relief because of possibility of teratogenic and long-term effects for the offspring.
2) Immunologic activity. Therefore, during long-term use of calcitonin, as is the case in treatment and prevention of osteoporosis, neutralizing antibodies are formed, that reduces effectiveness of use of calcitonin (Levy F et al., Formation of Neutralizing Antibodies During Intranasal Synthetic Salmon Calcitonin Treatment of Pagets Disease. 1988, 67, 3, 541-545).
3) Full-length calcitonins contain amyloidogenic sequence Gly2-Gln14 which is common for many amyloidogenic proteins (Steven S.-S. Wang1, Theresa A. Good2 and Dawn L. Rymer3).
4) The cost of full-length calcitonin synthesis and treatment with this preparation is very high. For that reason calcitonins are referred to orphan drugs which are used only when there are no alternative ways of treatment, for example, in case of Paget's disease (Maresca V. Human calcitonin in the Management of osteoporosis: A multicenter Study.—J. Int. Med. Res., 1985, 13, 311-316).
For the purpose of elimination of the specified disadvantages we have separated a fragment of salmon calcitonin which comprises 16-21 amino acids of salmon calcitonin (hereinafter referred to as CT16-21) called the “active centre” of calcitonin (G. P. Vlasov, V. R. Glushenkova, A. M. Kotin et al. (1989) “Search of Active Centre of Calcitonin”, Chemistry of Peptides and Proteins 4, 89) (SEQ ID NO: 12):
16  17  18  19  20  21Leu-His-Lys-Leu-Gln-Thr
It was shown that the natural fragment of salmon calcitonin, CT16-21 peptide, has high analgesic activity in the rat formalin test which allows identifying non-narcotic type of anesthesia, whereas it does not have immunologic activity, impact on calcium metabolism and does not contain amyloidogenic sequence. Comparison with similar sequences (16-21) of human, swine, bovine and rat calcitonins revealed greater activity as opposed to the latter ones. (A. M. Kotin, G. P. Vlasov et al. (1988) “Search of “active centre” and comparative study of full-length calcitonin and sequence 16-21 of different calcitonins in various physiological tests. Abstracts of the “Peptide Physiology” symposium”, Leningrad, 106).